Physiologists have long recognized that the hypothalamus controls all the secretory functions of the adenohypophysis with the hypothalamus producing special polypeptides which trigger the secretion of each pituitary hormone. A hypothalamic releasing factor has been characterized for the pituitary hormones thyrotropin and prolactin (i.e. the tripeptide TRF), for the pituitary gonadotropins, luteinizing hormone and follicle stimulating hormone (i.e. the decapeptide LRF, LH-RH or GnRH) and for the pituitary hormones .beta.-endorphin and adrenocorticotropin (i.e. the 41-amino acid polypeptide CRF). An inhibitory factor has also been characterized in the form of somatostatin which inhibits the secretion of growth hormone(GH). Each of these hypothalamic releasing factors and somatostatin have been reproduced by total synthesis, and many analogs of the native structures have been synthesized.
A corresponding hypothalamic releasing factor for pituitary GH has long been sought after, and a polypeptide has recently been isolated from an extract from a human pancreatic tumor, purified, characterized, synthesized and tested which promotes the release of GH by the pituitary. The sequence of the first 40 residues of this peptide is as follows: Tyr-Ala-Asp-Ala-Ile-Phe-Thr-Asn-Ser-Tyr-Arg-Lys-Val-Leu-Gly-Gln-Leu-Ser-Al a-Arg-Lys-Leu-Leu-Gln-Asp-Ile-Met-Ser-Arg-Gln-Gln-Gly-Glu-Ser-Asn-Gln-Glu-A rg-Gly-Ala. The peptide is believed to be and is hereinafter referred to as hpGRF (for human pancreatic tumor GH releasing factor).